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Biomedical subjects

T Sone

Publications and source records attributed to T Sone.

At least 181 records · Page 10Linked to original sources

Osteoclast-mediated osteolysis in bone metastasis from renal cell carcinoma.

Osteolytic characteristics of bone metastasis from renal cell carcinoma were morphologically and biochemically investigated. First, undecalcified ground sections of bone metastases were made from four patients with renal cell carcinoma. Second, renal cell carcinoma cell line (RCC-K1) was established from one of the four patients, and its effect on bone resorption in vitro was examined. Marked proliferation and activation of osteoclasts around the tumor cells was histologically demonstrated. Conditioned medium from the RCC-K1 cells contained potent bone-resorbing activity in vitro. The activity was reduced to basal level by calcitonin, but was not blocked by indomethacin. The activity was lost after dialysis (MW cutoff 3500), while it was retained after 2 weeks of storage. Levels of prostaglandin E2 and 1,25-dihydroxyvitamin D of the RCC-K1-conditioned medium were insufficient to cause bone resorption in vitro. The conditioned medium did not stimulate cAMP accumulation in rat osteoblastic cells. These results suggest that renal cell carcinoma causes bone destruction through the stimulation of osteoclasts by locally secreting an unknown humoral factor or factors.

Aged↗

The effect of RO15-1788 on cardiovascular depression caused by fentanyl and diazepam.

Cardiovascular depression occurring when diazepam is combined with fentanyl has been investigated using the benzodiazepine antagonist RO15-1788 in the dog. After the initial administration of fentanyl (40 mcg/kg), the mean arterial pressure (MAP) decreased to 89% of its control value. Following the administration of diazepam (1.2 mg/kg), the MAP and the total peripheral resistance (TPR) decreased significantly, to 75% and 83% of their control values respectively. After the administration of RO15-1788 (0.4 mg/kg), the MAP increased significantly to 90% and the TPR to 102% of their control values and, lastly, the administration of naloxone (40 mcg/kg) increased the MAP to 108% of its control value. No relationship was found between the changes in the catecholamines and the changes in the MAP after the administration of fentanyl, diazepam, and RO15-1788. The mechanism of circulatory depression when diazepam was used with fentanyl is interpreted as being a peripheral vasodilatory effect of diazepam acting by way of the benzodiazepine receptors since RO15-1788 was found to antagonize this effect.

Journal Article↗

Cadmium-induced synthesis of metallothioneins in human lymphocytes and monocytes.

Cd2+-binding proteins of peripheral blood lymphocytes and monocytes have not well been characterized so far, although they are expected to be a clue for understanding Cd2+ toxicity in those immune competent cells. We separated a family of Cd2+-binding proteins from Cd2+-exposed human peripheral blood lymphocytes by gel filtration chromatography, and characterized them by SDS-gel electrophoresis. The proteins showed electrophoretic behaviours closely similar to metallothioneins (MTs) of HeLa cells derived from human cervical carcinoma. The proteins were also found in Cd2+-exposed monocytes, and were inducible by Cd2+ in both lymphocytes and monocytes. Anti-MT serum specifically precipitated these proteins, which were thus identified as MTs. These results suggest that the two classes of the cells involved in the immune system possess a protective mechanism against Cd2+ through MTs. A variety of human lymphoid cell lines derived from both T and B cells were also found to have capacity to synthesize MTs in response to Cd2+.

Adult↗

Induction of metallothionein synthesis in Menkes' and normal lymphoblastoid cells is controlled by the level of intracellular copper.

A study was carried out on the uptake of copper, zinc, or cadmium ions and their induction of metallothionein synthesis in Menkes' and normal lymphoblastoid cells. The main difference between Menkes' and normal cells in the uptake of these metal ions was an increased uptake of copper ions in Menkes' cells at a low concentration of CuCl2 (2.1 microM). The CuCl2 concentration necessary to induce metallothionein synthesis in Menkes' cells was 50 microM, whereas that in normal cells was about 200 microM. The levels of zinc or cadmium ions needed to induce metallothionein in Menkes' cells were similar to those in normal cells. At least four isomers of metallothionein were induced by copper, zinc, and cadmium ions in both types of cells. Metallothionein synthesis in Menkes' and normal cells was induced when the amounts of intracellular copper reached a threshold level of approximately 0.2 nmol/10(6) cells, and the rate of metallothionein synthesis in these cells was increased as a function of the amounts of intracellular copper (0.2-1.7 nmol/10(6) cells). These results indicate that the induction of metallothionein synthesis in lymphoblastoid cells is controlled by the level of intracellular copper, suggesting that the major defect in Menkes' cells is not due to the abnormal regulation of metallothionein synthesis but to an alteration of the copper metabolism in cells by which the levels of intracellular copper become larger than those in normal cells and just lower than the threshold level for induction of metallothionein synthesis.

B-Lymphocytes↗

Metallothioneins of monocytes and lymphocytes.

Monocytes and lymphocytes were separated from human peripheral blood, and their capacity to synthesize metallothioneins (MTs) was examined. Both cell types can produce proteins electrophoretically similar to HeLa cell MTs. These proteins are inducible by Cd2+ and specifically precipitable by anti-MT serum. To have an insight into the capacity of T- and B-lymphocytes to produce MTs, sensitivity to Cd2+ of both cell types was estimated during mitogen-specific blastogenesis. Lymphocytes were prepared from mouse spleen and stimulated by concanavalin A (ConA) or lipopolysaccharide (LPS) in the presence of Cd2+. [3H]thymidine incorporation, as well as [3H]uridine incorporation in an earlier stage, was more severely inhibited by Cd2+ in ConA-induced mitogenesis than in LPS-induced mitogenesis, indicating T-lymphocytes are more sensitive to Cd2+ toxicity. This may reflect lower capacity of T-lymphocytes to synthesize MTs in response to Cd2+.

Animals↗

Reactive endosteal bone formation.

The microstructure of reactive endosteal new bone was examined using undecalcified ground sections in five pathologic conditions (bone metastasis from prostate cancer in seven cases, intervertebral osteochondrosis in five, Paget disease in four, chronic suppurative osteomyelitis in two, and fracture healing in one). To determine a basic form of rapid intramembranous bone formation, fetal rat calvaria and primitive bones made in clonal osteogenic cell culture were also observed. In slow bone-forming conditions, lamellar new bone was deposited on pre-existing trabecular surface and caused trabecular thickening on radiographs. In contrast, in rapid bone-forming conditions, woven bone was deposited as spicules extending from trabecular surface so as to form new networks in intertrabecular space. This causes obscurity of trabecular margins radiographically. Reactive endosteal bone formation may be nonspecific and have a significance for assessing the virulence of underlying pathologic conditions like periosteal reactions.

Aged↗

End plate of the discovertebral joint: degenerative change in the elderly adult.

Degenerative change at the end plate of the discovertebral joint was studied in the elderly adult by correlating the histologic and radiographic findings. Undecalcified ground sections were made from 21 autopsied lumbar spines that demonstrated no evidence of disease except age-related osteoporosis. Histologic examination showed that the cartilaginous end plates were degenerated to various extents and were replaced by subchondral bone proliferation (endochondral bone formation) in the direction of the joint space. In advanced cases, this histologic finding was reflected in radiographs as a subchondral sclerotic zone protruding toward the disk space. The degree of end-plate change was positively correlated with disk-space narrowing and the vacuum phenomenon (degeneration of the nucleus pulposus) but not with osteoporosis and vertebral compression. Anatomically and functionally, this may be the most common form of degeneration at the discovertebral joint end plate. Further study will be necessary to clarify the process.

Aged↗

Crystallization of Bowman-Birk type protease inhibitor (peanut) and its complex with trypsin.

Crystallization and preliminary crystallographic study of Bowman-Birk type protease inhibitors, A-I, A-II, and B-III from peanut seeds (Arachis hypogaea), and of the A-II + trypsin complex were carried out. A-II, with 70 amino acid residues, crystallizes in a trigonal system, P3(1)21 (or P3(2)21), a = 71.8, c = 65.9 A, Z = 12 or 18. The A-I crystal is isomorphous with that of A-II, indicating that the N-terminal residues are in a disordered state in both crystals. The B-III crystal is monoclinic, C2, a = 119.6, b = 69.6, c = 94.2 A, beta = 115.1 degrees, Z is about 40. The A-II + trypsin complex crystallizes in an orthorhombic system, P2(1)2(1)2(1), a = 55.5, b = 56.0, c = 182.1 A, Z = 4.

Arachis↗